Light delivery device using conical diffusing system and method of forming same

ABSTRACT

The present invention provides devices, methods of manufacture, methods of use and kits related to transmitting and diffusing light for delivery to a target site. Techniques are provided which allow accurate control of the illumination profile with a diffuser tip design which is easily produceable, relatively inexpensive and provides countless variations to obtain desired illumination profiles. This is achieved with the use of at least one scattering region having a conical shape. The number of conical scattering regions, the dimensions of such region(s), and the scattering properties of the scattering materials may be selected individually and/or collectively to selectively control the resulting illumination profile. In addition, the conical features allow for other beneficial design features, such as a smaller cross-sectional diameter than is typically achievable with other techniques. The resulting light transmission and diffusion apparatus is operable with a high efficiency, highly predictable illumination profile and ease of use.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to apparatus, methods of manufacture, andmethods of use for transmitting and diffusing light for delivery to atarget site to be illuminated, heated, irradiated, or treated byexposure to light. Particularly, the present invention relates to thedelivery of light to a body lumen or body cavity for photodynamictherapy of atherosclerosis, malignant or benign tumor tissue, cancerouscells and other medical treatments. Photodynamic Therapy (PDT) is aknown method of treating target regions or sites, such as tumors,atheromatous plaques and other tissues, in humans by administering aphotosensitizing substance to a patient and allowing it to concentratepreferentially in the target sites. It has been found that certainabnormal growths, such as certain cancerous tissue and atheromatousplaque, have an affinity for these photosensitizing agents.Photosensitizing agents are compounds that, when exposed to light, orlight of a particular wavelength or wavelengths, create O₂ radicalswhich react with the target cells. Examples of such agents includetexaphyrins, hematoporphyrin, chlorins, and purpurins. In the case ofliving cells, such as cancer tumors, an appropriate photosensitizingagent is used to create the O₂ radicals which kill the target cells. Inother situations, such as when it is desired to destroy atheromatousplaque tissue, an appropriate photosensitizing agent is activated todestroy the plaque by lysis (breaking up) of such plaque. Mechanismsother than lysis, e.g. cell apoptosis, may also be involved.

Photoactivation of the photosensitizer is achieved by locally deliveringlight to the target region, preferably in a manner which achieves anoptimum “dose” and emission configuration which is consistent with thevolume and geometry of the target tissue. This may be accomplishedthrough the use of light delivery systems which utilize optical fibers.For example, for tubular body areas and lumens, such as a bronchus,esophagus or blood vessel, it is common to use a fiber optic diffuserwhich distributes the light in a cylindrical pattern. Thus, for PDTtreatment of esophageal cancer, an optical fiber may be equipped with anapparatus at its tip which disperses light propagating along the fiberin a uniform cylindrical pattern with respect to the central axis of theoptical fiber. Uniformity is usually desired to ensure delivering aknown and optimum dose.

A number of diffuser tip designs have been developed to produce acontrolled and generally uniform profile of illumination. One approachinvolves modifying a distal segment of the waveguide, typically anoptical fiber. Such modifications include etching the fiber cladding orcreating fiber gratings within the fiber core. Another approach involveslaunching light from the tip of a waveguide into a diffuser tipcontaining scattering medium, wherein the light is launched in aprimarily axial direction and is distributed radially outward by theoptical scattering medium. Often it is desired that the scatteringmedium have a uniform scattering property. Thus, many designs aim touniformly embed scattering particles throughout an optically clearmedium. In addition, a mirror is often placed at the distal end of sucha diffuser tip to reflect light which has not been sufficiently diffusedduring its first pass through the scattering medium.

Although the scattering medium approach typically produces more robustand highly flexible diffuser tips, a number of difficulties arise withthis approach. First, uniform light distribution is difficult to achievewith current designs when the diffuser tip is long and narrow,particularly if the tip is desired to be flexible. Second, theillumination profile may only be controlled by one parameter for a giventip length, the diffusion property of the scattering medium. This makesit difficult to obtain a uniform “top hat” illumination profile withsharply demarcated edges. Third, if a high quantity of light is reachesthe mirror, the mirror absorbs some of the light and can consequentlywarm up. High quality mirrors with dielectric coatings and no edgeimperfections are needed to reduce such warming. And fourth, fixing amirror at the end of a flexible and soft scattering medium to providecontrolled reflection properties is often difficult to achieve,particularly in small diameter diffuser tips (e.g. less than 0.18 inchesor 450 μm). Such small diameter tips may be used in treatingobstructions in the coronary arteries and may require a diffuser tip ofapproximately 0.14 inches (350 μm) or less.

To overcome some of these difficulties, diffuser tip designs haveutilized a light scattering medium having continuously increasingoptical scattering power in a direction parallel to the central axis ofthe tip in attempts to maintain uniform circumferential scatteringpower. The increasing scattering power is obtained by continuousvariation of the concentration of scattering particles embedded in thecore medium along the length of the tip. However, there are practicaldifficulties in obtaining both the uniform circumferential scatteringpower and the continuously increasing scattering power along the lengthof the tip. In an effort to overcome these difficulties, discontinuoussections of scattering medium have been used along the length of thetip, each section having an increased scattering power. With thisdesign, circumferentially uniform scattering power is still difficult toobtain since the discontinuous sections do not provide smoothtransitions. In addition, if this design is used without a reflectingmirror at the end of the diffusing medium, a large number of discretesections of scattering medium are required.

For these reasons, it would be desirable to provide a light transmissionand diffusion apparatus which overcome at least some of the shortcomingsdiscussed above. In particular, it would be desirable to provide such anapparatus having a diffuser tip which delivers a uniform illuminationprofile by means of a design which is practically achievable,manufacturable, and controllable. It would be further desirable toprovide such a diffuser tip design which is easily adapted to provideother desired illumination profiles. In addition, such designs should beadaptable to various dimensional parameters, particularly small outerdiameter for access to small vessels, such as coronary arteries. Thismay include the elimination of a reflective mirror fixed at the end ofthe diffuser tip and/or the addition of a guidewire lumen. Further, itwould be desirable to provide methods of manufacture, methods of use andkits related to such an apparatus.

2. Description of the Background Art

Anderson (U.S. Pat. No. 5,814,041) describes an illuminator comprising adifferential optical radiator having two regions, each having differentreflectivities and therefore transmissivities, and a laser fiberdisposed within the differential optical radiator. The laser fiberincludes a diffusively reflective coating. The radiator is described toproduce a substantially uniform pattern of illumination from said firstand second regions.

Hashimoto (EP 673627) and Hashimoto et al. (U.S. Pat. No. 6,152,951)describe a cancer therapeutic instrument having an optical fiberemitting from its tip activation light toward scatter member.

Sinofsky (WO 96/07451) describes a diffusive tip apparatus for use withan optical fiber for diffusion of radiation propagating through thefiber. Related U.S. Pat. No. 5,632,767 describes an apparatus having atip assembly for directing radiation outward wherein each tip assemblyis arranged in a loop configuration to form a loop diffuser. U.S. Pat.No. 5,637,877 describes an apparatus for sterilizing an endoscopicinstrument lumen. U.S. Pat. No. 5,643,253 describes an apparatus havinga sheath surrounding an optical fiber having a fluted region which iscapable of expanding upon penetration of the optical fiber intobiological tissue. And U.S. Pat. No. 5,908,415 describes an apparatushaving a tip assembly which relies on a reflective end surface toretransmit some of the light back through the scattering mediumproviding an axial distribution over the length of the scatterer tubewhen combined with the initially scattered light.

Esch (U.S. Pat. No. 5,754,717) claims a device for diffusing lighthaving a tip composed of a material characterized by low lightabsorption to avoid producing a hot tip.

Mersch (U.S. Pat. No. 5,693,049) describes an apparatus comprising atubular catheter and an optical coupler for coupling light radiation tothe catheter, which diffuses the light radiation outwardly therefromwithin a blood vessel to irradiate blood flowing through the bloodvessel.

Overholt (WO 9743966) describes a device that is able to irradiate asegment of tissue that is 4 cm or longer. Overholt et al. (U.S. Pat. No.6,146,409) describes a balloon catheter having a treatment window, thatis at least 4 cm in length, and a diffuser that extends beyond thedistal and proximal ends of the treatment window. The window anddiffuser function or cooperate together to provide uniform light in asingle effective dose.

Narciso (U.S. Pat. No. 5,169,395) describes a guidewire-compatibleintraluminal catheter for delivering light energy in a uniformcylindrical pattern.

Fuller (U.S. Pat. No. 5,807,390) describes a probe having a tipconsisting essentially of light propagating material having inclusionsdistributed therein and generally throughout; the light propagatingmaterial being a light propagating inorganic compound, wherein theinclusions include microscopic voids having dimensions substantiallysmaller than the wavelength of the light energy.

Doiron (U.S. Pat. No. 5,269,777) describes a diffuser tip comprising anoptical fiber and a terminus comprising a second core consisting of asubstantially transparent elastomer which is concentrically surroundedby a layer having light-scattering centers embedded therein.

Willing (DE 4,329,914) describes a linear optical waveguide havingcut-out elements arranged at surface and/or in volume of light waveguidewhich allow part of rays in waveguide to emerge from waveguide.

Rowland (WO 9000914) describes a device for illuminating a flexiblestricture in a tube, comprising an illuminator body provided with atransparent window and adapted to be passed down the tube and a lightsource in the illuminator body, for illuminating the window theilluminator body being so adapted that a known quantity of light can bedirected onto the stricture.

Kakarni (U.S. Pat. No. 5,078,711) describes a laser irradiation devicehaving a changeable irradiation angle of laser light.

Additional patents relating to light delivery devices and methodsinclude U.S. Pat. Nos. 5,903,695; 5,871,521; 5,861,020; 5,851,225;5,836,938; 5,833,682; 5,797,868; 5,766,222; 5,728,092; 5,723,937;5,718,666; 5,709,653; 5,700,243; 5,695,583; 5,695,482; 5,671,314;5,645,562; 5,620,438; 5,607,419; 5,588,952; 5,542,017; 5,536,265;5,534,000; 5,530,780; 5,527,308; 5,520,681; 5,514,669; 5,496,308;5,479,543; 5,478,339; 5,456,661; 5,454,794; 5,454,782; 5,453,448;5,441,497; 5,432,876; 5,431,647; 5,429,635; 5,401,270; 5,373,571;5,372,756; 5,363,458; 5,354,293; 5,348,552; 5,344,419; 5,337,381;5,334,206; 5,330,465; 5,312,392; 5,303,324; 5,292,320; 5,267,995;5,253,312; 5,248,311; 5,219,346; 5,217,456; 5,209,748; 5,207,669;5,196,005; 5,193,526; 5,190,538; 5,190,535; 5,151,096; 5,139,495;5,129,897; 5,119,461; 5,074,632; 5,073,402; 5,059,191; 5,054,867;5,042,980; 5,032,123; 4,995,691; 4,989,933; 4,986,628; 4,927,231;4,889,129; 4,878,725; 4,878,492; 4,860,743; 4,848,323; 4,842,390;4,840,174; 4,782,818; 4,763,984; 4,736,745; 4,733,929; 4,732,442;4,693,556; 4,693,244, 4,676,231; 4,660,925; 4,612,938; 4,528,617;4,471,412; 4,466,697; 4,422,719; 4,420,796; 4,336,809; 4,248,214;4,195,907; Re 34544.

Additional foreign patents and applications relating to light deliverydevices and methods include WO 9923041; WO 9911323; WO 9911322; WO9904857; WO 9848690; WO 9811462; WO 9743965; WO 9629943; WO 9607451; WO9509574; WO 9325155; WO 9321841; WO 9321840; WO 9318715; WO 9004363; WO9002353; EP 772062; EP 732086; EP 732085; EP 732079; EP 292621; EP394446; EP 391558; EP 433464; EP 377549; EP 561903; EP 6022051; DE2853528 DE 19507901; GB 2323284; GB 2154761; JP 5011852; AU-A-64782/90.

SUMMARY OF THE INVENTION

The present invention provides devices, methods of manufacture, methodsof use and kits related to transmitting and diffusing light for deliveryto a target site. Such delivery of light is useful in PhotodynamicTherapy (PDT), a method of treating target sites in the human body, suchas tumors, atheromatous plaques and other disease tissues. Typically,intraluminal, intracavity, or interstitial PDT is performed with the useof a light guide having a diffuser tip located at its distal end. Lighttraveling axially through the light guide is then radially dispersedthrough the diffuser tip to treat the target site. The present inventionachieves accurate control of the illumination profile with an improveddiffuser tip design which is easily produceable, relatively inexpensiveand provides countless variations to obtain desired illuminationprofiles. The diffuser comprises at least one scattering region having aconical shape. The number of conical scattering regions, the dimensionsof such region(s), and the scattering properties of the scatteringmaterials, among other features, may be selected individually and/orcollectively to selectively control the resulting illumination profile.Uniform illumination profiles which are typically difficult toaccurately produce may be more easily achievable with the techniques ofthe present invention. Further, alternative profiles may also beachieved by altering design choices in a controlled manner. In addition,the conical features allow for other beneficial design features, such asa smaller cross-sectional diameter than is typically achievable withother techniques. The resulting light transmission and diffusionapparatus is operable with a high efficiency, highly predictableillumination profile and ease of use.

In a first aspect of the present invention, a light transmission anddiffusion apparatus is provided for use in delivering light to a targetsite, such as for treatment or diagnostic purposes. The apparatuscomprises a light guide which transmits light from a light source to adiffuser tip. The diffuser tip diffuses the received light in acontrolled pattern, described as an illumination profile. Delivery ofthe diffused light to the target site provides specific treatmentdepending on the profile, duration and intensity of the light. Thus,various embodiments of the diffuser tip provide different illuminationprofiles and therefore different treatment and/or diagnostic options.

In a first embodiment, the light guide has a proximal end and a distalend, the proximal end adapted for coupling to a light source and adistal end having a light transmitting end portion. In addition, thediffuser tip has a proximal end, enclosing the light transmitting endportion, and a distal end. The tip comprises a number of regions, eachregion having a specific shape, dimension and material to create anoptical effect. Each tip comprises at least two regions. The firstregion may be of any shape and may comprise any suitable medium, such asa transparent material or a light scattering medium. The second regionhas a conical shape and is comprised of a light scattering medium or apartially light scattering and partially light absorbing medium.Although the second region may be distal to the first region, the secondregion is proximal to the distal end of the diffuser tip. In otherwords, the distal end of the diffuser tip may have any shape, square,round, conical or other, but the second region is separate from andproximal to this distal end. Thus, if the diffuser tip has a conicallyshaped distal end having an apex, the diffuser tip will also have aconically shaped second region which is separate from this having itsown apex. Such an example would be a diffuser tip having a conicallyshaped second region, with its apex facing the light transmitting endportion, and a conically shaped distal end facing distally.

By providing a diffuser tip comprising a conically shaped region havinglight scattering properties, light entering the diffuser tip is diffusedand redirected in a unique manner which affords a number of advantages.To begin, since the conical region varies in dimension from its apex toits base, light will enter or exit the conical region in a gradualpattern. This affords a smoother transition between regions havingdifferent scattering powers. In addition, the conical shape provides aneffective “overlap” or nesting of regions having different scatteringproperties. Thus, light scattered radially outward from the axial centerof the diffuser tip may be directed through more than one scatteringmaterial adding higher levels of scattering control. By adding morecones, and thus more layers, the scattering effect may be more highlydefined and manipulated. Likewise, by varying the scattering materialsin the cones, the scattering effect may be additionally manipulated.Thus, a number of illumination profiles may be created depending on thetype, number, nesting and arrangement of the conical scattering regions.

In preferred embodiments, the conical second region is oriented so thatits apex is directed toward the light-transmitting end portion. Thus,the conical region increases in width toward the distal end of thediffuser tip and therefore its scattering power naturally increasesmonotonically. This design provides a high efficiency or ratio betweenthe light power emitted from diffuser tip and the light power coupled tothe proximal end of the light guide. Most light is propagated throughthe tip and a minimum quantity is emitted back to the light guide bybackscattering induced by the cone. Simulations and experiments haveshown that introduction of a conical region in this orientation does notaffect the light distribution proximal to the apex and only causes localeffects in the area of the cone. It may be appreciated that in otherembodiments the conical second region is oriented in a direction otherthan toward the light-transmitting end portion. In this case, least someof the above described advantages are still afforded.

As mentioned, additional regions, such as a third region, fourth region,fifth region, sixth region, seventh region, eighth region, ninth region,tenth region or more, can be included in the diffuser tip. Suchadditional regions may have any shape and may be comprised of anymedium, including transparent material, light absorbing, lightscattering mediums and mediums which partially scatter and partiallyabsorb. Although more than one region in a diffuser tip may be comprisedof the same material having the same concentration of scatteringparticles, and therefore the same scattering power, each such region isseparated by a region having a different scattering power. In someembodiments, the additional regions have a conical shape and areoriented so that each apex is directed toward the light-transmitting endportion. Typically, these conical regions have bases which are alignedand apexes which are disposed at different distances from the basesthough each pointing toward the light-transmitting end portion.

Also, in some embodiments, each region has an increasing scatteringpower in the direction of the distal end. This may be achieved by theincorporation of higher and higher concentrations of scatteringparticles in each region toward the distal end. This may culminate inthe distal end being opaque wherein any remaining unscattered light willnot pass through the distal end. This design may eliminate the need fora mirror placed at the distal end of the diffuser tip. Typically suchmirrors reflect light from the distal end back toward the lighttransmitting end portion. However, this increases inefficiency, can leadto heating of the mirror and is difficult to manufacture, particularlywith diffuser tips having small cross-sectional diameters.

Thus, as described above, the diffuser tip may be comprised any numberof regions wherein at least one has a conical shape with lightscattering properties. Such regions may be arranged in any orientationand may be comprised of any light scattering, transparent or othermaterial. Other materials may include particles providing opticalproperties other than or in addition to scattering, such as lightabsorbing particles, fluorescent particles, or magnetic resonanceimaging (MRI)-detectable particles. Such optical properties may allowthe region to be used for detectors, sensors or MRI-guided placement ofthe diffuser tip, in addition to light therapy treatment. This mayreduce the need for fluorscopy in placement of the diffuser tip. In apreferred embodiment, the diffuser tip is comprised of a first regiondisposed adjacent to the light transmitting end portion and a number ofadditional regions, each conical in shape and oriented so that theirapexes are directed toward the end portion.

In any case, the apparatus provides an illumination profile resultingfrom the design choices of the regions within the diffuser tip. In oneembodiment, the regions are positioned and their light scatteringmediums and concentrations of scattering particles are chosen such thatthe diffuser tip produces a substantially uniform pattern of lightemission. Alternatively, the regions may be shaped, arranged andcomprised of specific mediums which will provide different illuminationprofiles. For example, the light intensity may be increased near theproximal and distal ends relative to a plateau of lesser intensitytherebetween. This profile may compensate for effects near the ends ofthe diffuser tip which would otherwise provide diminished lightintensity at the target tissue. Thus, any desired illumination profilemay be achieved by altering the shape, size, arrangement, orientation,choice of scattering medium, concentration of scattering particles andother variables related to the regions within the diffuser tip.

In second aspect of the present invention, the light transmission anddiffusion apparatus may include additional optional features. First, theapparatus may include markings which are used for visualization purposesduring treatment. Marking may include radiopaque markings, bands orcoatings which are visible under fluoroscopic conditions. Typically suchmarkings are positioned close to a region having light scatteringproperties, such as near one end, the other end or both ends of theregion. Alternatively, one or more regions may be comprised of amaterial which provides radiopacity, such as barium. Second, theapparatus may include a guidewire lumen. Typically, the guidewire lumenis disposed along an axis which is offset from the central axis of theapparatus. For example, the guidewire lumen may be positioned outside ofthe scattering regions of the diffuser tip, possibly along the outsideedge of the apparatus. The guidewire lumen may extend from the distalend of the diffuser tip to any location along the apparatus. In anycase, when a guidewire lumen is present, a guidewire will be positionedwithin the guidewire tubing during delivery of light therapy to thetarget site. In the area of the diffuser tip, the guidewire tubing iscomprised of a transparent material that allows passage of visible lightso that the guidewire tubing will not interfere with the delivery oflight to the target region.

In a third aspect of the present invention, the light transmission anddiffision apparatus may be adapted to be introduced through otherdevices or instruments. For example, the diffuser tip may be adapted tobe insertable within a lumen in a catheter. Such a catheter may be atransit catheter or a balloon catheter. Such procedures will bediscussed in more detail related to methods of the present invention.

According to the methods of manufacturing the present invention, thelight transmission and diffusion apparatus is processed by a number ofsteps. One step involves providing a segment of external tubing having aproximal end, a distal end and a lumen therethrough having a centeraxis. In addition, the segment has a light guide having an lighttransmitting end portion disposed within the tubing so that there is aluminal space between the end portion and the distal end. It isprimarily within this luminal space that the above described regionswill reside. Thus, another step involves creating a first region byinjecting a first medium into the luminal space from the distal end.And, still another step involves creating a second region by injecting asecond medium into the distal end wherein the second region has aconical shape. When the step of creating the second region is performedafter the step of creating the first region, the second mediumessentially pushes the first medium through the tubing toward the lighttransmitting end portion. Due to the flow dynamics in a tube, thevelocity of the flowing material reaches a maximum near the central axisof the lumen. Since the second medium is traveling at a higher velocitynear the central axis, the second region forms a conical shape whereinthe apex is directed toward the end portion. This process can berepeated by adding a third region by injecting a third medium into thedistal end wherein the third region has a conical shape. Similarly,additional regions may be added by similar injection steps. The lengthand shape of the cones may be controlled by the method of injection,including speed of injection, angle and position of the injection tubeand a variety of other variables. In addition, it may be appreciatedthat regions may be non-conical shaped by using other methods ofinjection. Further, conical regions, wherein the apex is not directedtoward the end portion may be produced by injecting material through thetubing wall toward the distal end or by producing the diffuser tipitself and then connecting the diffuser tip to the light guide.

It may be appreciated that the light guide may be comprised of anoptical fiber. In this case, the optical fiber may be comprised of acylindrical core, a cladding layer surrounding the cylindrical core, anda protective buffer encasing the cladded fiber. In this case, a lengthof the buffer will be removed from the light transmitting end portion,to reveal a length of the cylindrical cladded core.

According to the methods of the present invention, the apparatus of thepresent invention may be used for performing photodynamic therapy at atarget site within a body, such as interstitially or within a body lumenor cavity. Photodynamic therapy involves the use of photosensitivecompounds which are introduced to the target site prior to lightdelivery. Typically the photosensitizing agents are administered to thepatient and allowed to concentrate preferentially in the target siteswhich have an affinity for the agents. The light transmission anddiffusion apparatus of the present invention is then introduced to thetarget site and light radiation is coupled to the apparatus so thatlight transmitted and received by the diffuser tip is delivered to thetarget site. Such introduction may be accomplished in a number of ways.When the body lumen is a blood vessel, the introducing step may furthercomprise advancing the distal end of the apparatus through thevasculature from a location remote from the target site. This locationmay be accessed percutaneously, such as using needle access as in theSeldinger technique, or by performing a surgical cut down procedure orminimally invasive procedure.

The apparatus may also be introduced to the target site through anotherdevice or apparatus. For example, a catheter having a lumen therethroughmay first be positioned within the target site. The light transmittingand diffusing apparatus may then be introduced through the catheterlumen so that the diffuser tip is also positioned within the target. Theapparatus may then deliver light to the target site wherein the light isdispersed through the walls of the catheter. Alternatively, the cathetermay be retracted while the apparatus remains in place. In anotherexample, a balloon catheter having a balloon mounted on its distal endmay be positioned within the target site. In this example, target sitemay comprise an atheromatous stenosis and the balloon catheter is usedto perform an angioplasty procedure. While the balloon is inflated, theapparatus may be introduced through the balloon catheter so that thediffuser tip is also positioned within the target site. The apparatusmay then deliver light to the target site wherein the light istransmitted through the balloon. Alternatively, the balloon may bedeflated and the balloon catheter may be retracted while the apparatusremains in place.

The methods and apparatuses of the present invention may be provided inone or more kits for such use. The kits may comprise a lighttransmission and diffusion apparatus and instructions for use.Optionally, such kits may further include any of the other systemcomponents described in relation to the present invention and any othermaterials or items relevant to the present invention.

Other features and advantages of the invention will appear from thefollowing description in which the preferred embodiments have been setforth in detail in conjunction with the company drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view illustration which depicts an embodiment ofthe light transmission diffusion apparatus of the present invention.

FIGS. 2-4 provide side views of various embodiments of the diffuser tipof the present invention.

FIG. 5 illustrates the diffusion of light rays delivered from the lighttransmission diffusion apparatus.

FIG. 5A illustrates light scattered from a conical region.

FIGS. 6A-6B are graphical representations of possible scattered lightillumination profiles deliverable by the apparatus.

FIGS. 7A-7C illustrate example distal end shapes of the diffuser tip.

FIGS. 8-10 provide side views of additional embodiments of the diffusertip of the present invention.

FIGS. 11A-11E illustrate how the present invention may be processed inmanufacturing.

FIG. 12 depicts an embodiment of the apparatus including a guidewirelumen.

FIG. 13 illustrates a cross-sectional view of a target site within bodylumen.

FIG. 14 illustrates methods of delivering light to a target site withthe use of the apparatus of the present invention.

FIGS. 15A-15B depict steps of including the use of a catheter in themethods of introducing the apparatus of the present invention.

FIGS. 16A-16B depict steps of including a balloon catheter in themethods of introducing the apparatus of the present invention.

FIG. 17 illustrates a kit constructed in accordance with the principlesof the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides for the transmission and diffusion oflight to a target site. This is achieved with the use of a lighttransmission and diffusion apparatus 100, an embodiment of which isillustrated in FIG. 1. In this embodiment, the apparatus 100 comprises alight guide 102 having a proximal end 104 and a distal end 106, theproximal end 104 adapted for coupling to a light source 110 and thedistal end 106 having a light-transmitting end portion 112. In addition,the apparatus 100 comprises a diffuser tip 120 having a proximal end 122enclosing the end portion 112 and a distal end 124. The tip comprises atleast a first region 126 and a second region 128, wherein the secondregion 128 has a conical shape. Optionally, the apparatus 100 may alsoinclude radiopaque markers 130, possibly one located near the proximalend 122 and one near the distal end 124 of the diffuser tip 120 asshown, to aid in visualization during use. Typically, as shown, theapparatus 100 has an elongated, cylindrical shape with a blunt or curveddistal end. Such a shape is adapted for use in treating cylindricaltarget locations, such as body lumens, or in reaching target locationswhich are accessible by similarly shaped pathways. Alternatively, theapparatus 100 may have other shapes conducive to other purposes.Further, the distal end 124 may have various shapes depending on usage.In general, the apparatus 100 is usually approximately 2-5 meters intotal length with an outer diameter of 100 microns to 2 mm, preferablyat least 2001 μm. The diffuser tip is typically approximately 1-15 cm inlength.

FIGS. 2-4 provide side views of various embodiments of the diffuser tip120. Referring to FIG. 2, the diffuser tip 120 is shown including itsproximal end 122 and distal end 124. The light-transmitting end portion112 of the light guide 102 is shown disposed within the proximal end122. Typically, the light guide comprises an optical fiber having abuffer layer which is stripped back to create the light-transmitting endportion. External tubing 150 provides a housing for the diffuser tip 120which contains one or more light scattering mediums. In this embodiment,two regions are shown, a first region 152 comprising a transparentmaterial having no scattering properties and a second region 154comprising a light scattering medium. Examples of light scatteringmediums include titanium dioxide, barium sulfate, powder quartz (SiO₂),aluminum oxide (Al₂O₃), polystyrene microspheres, silica microspheres,powdered diamond, zirconium oxide, ditantalum pentoxide, calciumhydroxyapatite, and a combination of any of these to name a few. Inaddition, the light scattering mediums may include particles whichprovide optical properties other than scattering. Such opticalproperties may allow the region to be used for detectors, sensors orMRI-guided placement of the diffuser tip, in addition to light therapytreatment. This may reduce the need for fluorscopy in placement of thediffuser tip. Examples of such particles include light absorbingparticles, fluorescent particles, or magnetic resonance imaging(MRI)-detectable particles, such as Motexafin Gadolinium. In each case,the light scattering medium comprises a base material within which isembedded scattering particles 156. Generally, materials having higherconcentrations of scattering particles 156 provide higher scatteringpower. In addition, certain types and sizes of scattering particles 156may provide higher scattering power when in the same concentration. Inthis embodiment, the second region 154 has a conical shape wherein itsapex 158 is directed toward the light transmitting end portion 112.

Referring to FIGS. 3-4, embodiments of the diffuser tip 120 may includemore than two regions, each region having different concentrations oflight scattering particles ranging from no particles to approximately5-15% particles. It may be appreciated that the quantity of particlesused depends on the type of the particles, the type of the base materialand the relative size of the particles to the delivered wavelength oflight. FIG. 3 illustrates an embodiment having a first region 160, asecond region 162 and a third region 164, each region comprised of lightscattering mediums having a different concentration or type of lightscattering particles 156. Differences in concentration or type areillustrated by differences in particle density and size. As illustrated,the first region 160 has the lowest concentration of scatteringparticles 166, the second region 162 has a higher concentration ofscattering particles 168 and the third region 164 has a similarconcentration but different type of scattering particles 170 relative tothe second region 162. In this example, the scattering power of thediffusive tip 120 increases from the proximal end 122 to the distal end124. In addition, the second region 162 and third region 164 are conicalin shape, each having their respective apex 158 directed toward thelight-transmitting end portion 112.

FIG. 4 illustrates an embodiment having a first region 170, a secondregion 172, a third region 174, a fourth region 176 and a fifth region178. Again, each region is comprised of light scattering mediums havinga different concentration or type of light scattering particles 156.And, differences in concentration or type are illustrated by differencesin particle density and size. As shown, two regions, such as the firstregion 170 and the fourth region 176 may have the same type and/orconcentration of scattering particles if they are separated by anotherregion, such as the second region 172. In addition, two regionscontaining scattering particles, such as the second region 172 and thefourth region 176, may be separated by a region having no scatteringparticles, such as the third region 174. Thus, any combination ofregions may be used to create a diffuser tip 120 having uniquescattering properties and hence illumination profile. In addition, inthe embodiment, the second region 172, third region 174, fourth region176 and fifth region 178 are all shown as having conical shapes withtheir respective apex facing the light-transmitting end portion 112.Although this orientation of the conical regions is preferred, it is notnecessary and other embodiments having different orientations will bediscussed in later sections.

FIG. 5 illustrates the diffusion of light rays 200 (illustrated asarrows) which are transmitted from a light source, delivered from thelight guide and diffused through the diffuser tip 120. A majority of thelight rays 200 are shown exiting the light transmitting end portion 112.Rays 200 which travel axially along the diffuser tip 120 are redirectedby interference with scattering particles, as shown. The light generallyexits within a cone which half angle is determined by the numericalaperature of the fiber. Although scattered rays are illustrated asdirected at a right angle to the axis, it may be appreciated thatscattered rays are directed in substantially all directions. Thisembodiment of the diffuser tip 120 includes a first region 202comprising a first medium having a first concentration of scatteringparticles, a second region 204 comprising a second medium having asecond concentration of scattering particles, and a third region 206comprising a third medium having a third concentration of scatteringparticles. As shown, rays 200 entering the first region 202 arescattered by the scattering particles. In this embodiment, rays 200continuing to the second region 204 are scattered to a higher degree dueto a higher scattering power of the second medium. Since less rays 200enter the second region 204 compared with the first region 202, thescattered output may be approximately the same from the two regions. Inaddition, the conical shape of the second region 204 provides both agradual transition between the scattering powers of the two regions andan interface which scatters the rays 200 in a desirable fashion.Referring to FIG. 5A, a light ray 200 entering a conical region 231having scattering properties will be scattered by the region 231 at itssurface 233 (interface) with a Lambertian (cosine) angular distribution.Consequently, a majority of the light rays 200 are scattered radially bythe conical region 231 and minimal rays 200 are backscattered toward thetip 235 of the conical region 231 and therefore the fiber end. Thus, theconical shape results in a highly efficiency diffuser tip.

Referring back to FIG. 5, rays 200 continuing to the third region 206are scattered to a higher degree due to a higher scattering power of thethird medium. Since less rays 200 enter the third region 204 comparedwith the first region 202 and second region 204, the scattered outputmay be approximately the same all three regions. And, the conical shapeof the third region 206 again provides both a gradual transition betweenthe scattering powers of the two regions and an interface which scattersthe rays 200 in a desirable fashion. Thus, the regions may be shaped,arranged and comprised of specific mediums which will effectivelyscatter substantially all light rays 200 entering the diffuser tip 120before the rays 200 reach the distal end 124. Thus, all lighttransmitted to the most distally positioned region is substantiallydiffused outwardly. In this case, there would be no need to fix areflective mirror at the distal end 124. The elimination of the mirrorprovides a number of benefits both in manufacture of the diffuser tip120 and in use of the apparatus 100. In particular, such elimination ofa need for a reflective mirror allows the diffuser tip 120 to be easilymanufactured having a maximum outside diameter in the range of 100 μm to2000 μm, preferably 250 μm to 1200 μm, more preferably 250 μm to 500 μm,including 0.014 inches (350 μm) which would allow introduction of thetip 120 into human coronary arteries or 0.018 inches (450 μm), or morepreferably 800 μm to 1200 μm.

FIG. 6A illustrates a graphical representation of a scattered lightillumination profile 260 or pattern of illumination from a diffuser tip120 such as from the embodiment shown in FIG. 5. The profile 260illustrates the light intensity of the scattered light rays relative tothe distance from the light guide measured axially along the diffusertip 120. As shown, the diffuser tip 120 provides a substantially uniformillumination profile 260, within approximately +/−20% uniformity. Lightexiting the diffuser tip 120 has essentially the same intensity fromnear the proximal end 122 to near the distal end 124 of the diffuser tip120. This is illustrated by the plateau 262 between the side edges 264.Alternatively, the regions may be shaped, arranged and comprised ofspecific mediums which will provide different illumination profiles. Forexample, as shown in FIG. 6B, the light intensity may be increased nearthe proximal and distal ends 122, 124, as illustrated by peaks 266,relative to a plateau 268 of lesser intensity therebetween. This profile261 may compensate for effects near the ends 122, 124 of the diffusertip 120 which would otherwise provide diminished light intensity. Thus,any desired illumination profile may be achieved by altering the shape,size, arrangement, orientation, choice of scattering medium,concentration of scattering particles and other variables related to theregions within the diffuser tip.

Example embodiments of the distal end 124 of the diffuser tip 120 areillustrated in FIGS. 7A-7C. The distal end 124 may have a shape adaptedfor use in treating specific target locations. Typically, such a shapeis adapted for use in treating body lumens or in reaching targetlocations which are accessible by lumen shaped pathways. For suchuseage, a rounded or curved shaped distal end 124 a may be desired, asshown in FIG. 7A. Or, a short, smooth, tapered distal end 124 b may bedesired, as shown in FIG. 7B. And in some cases, an extended, floppydistal end 124 c or narrow elongated portion which is floppy may bedesired, as shown in FIG. 7C, comprised of a flexible material toprovide a floppy feel such as provided by a guidewire. In preferredembodiments, the floppy distal end 124 c has a length of at least 10 mm.In each of these example embodiments, the distal end 124 is shaped toreduce any possible trauma to the body lumen or tissue of the targetlocation upon delivery of the diffusion apparatus 100. Also, each ofFIGS. 7A-7C illustrate the distal end 124 adjacent to a radiopaquemarker 130 which is positioned near the end of the external tubing 150having a first region 127 and second region 125 of scattering materialtherein. It may be appreciated that such features of the apparatus 100are illustrated for the purposes of example only and any shaped distalend 124 may be present with or without a radiopaque marker 130 orvarious regions of scattering materials, etc. It may also be appreciatedthat embodiments illustrated throughout may have any shaped distal endand are not limited to the shaped illustrated, often a flat end.

Additional embodiments of the diffuser tip 120 are illustrated in FIGS.8-10. Until this point, embodiments have been shown with all regions,aside from the region adjacent the light transmitting end portion 112,as conical in shape having an orientation in which the apex 158 isdirected toward the end portion 112. However, such shape, orientationand arrangement are not necessary for all regions. In the embodimentshown in FIG. 8, the diffuser tip 120 is comprised of a first region300, a second region 302, a third region 304, a fourth region 306 and afifth region 308. Each region may be comprised of different lightscattering mediums, each having a different concentration and/or type oflight scattering particles, no light scattering particles or the sameconcentration or type but separated by a region of a differentconcentration or type of particles. As shown, regions, such as thesecond region 302 and the fifth region 308, may be square or rectangularin shape while regions, such as the fourth region 306 may be conical inshape. Similarly, as shown in FIG. 9, which has a first region 310, asecond region 312, a third region 314 and a fourth region 316, a conicalregion may be oriented so its apex 158 is directed toward the distal end124, as illustrated by the first region 310. This may be combined withconical regions which are oriented so their apexes 158 are directedtoward the end portion 112, as illustrated by the third and fourthregions 314, 316.

Referring to FIG. 10, any region may be comprised of a light scatteringmedium having a concentration of light scattering particles which is notuniform. For example, in this embodiment, having a first region 320, asecond region 322, and a third region 324, the first region 320comprises a light scattering medium having light scattering particleswhich increase in concentration toward the distal end 124 of thediffuser tip 120. This may be combined with regions, such as the secondregion 322 and the third region 324 which have uniform concentrations ofscattering particles. In addition, in all embodiments of the diffusertip 120, the external tubing 150 may also have scattering properties.

FIGS. 11A-11E illustrate how the present invention may be processed inmanufacturing. Referring to FIG. 11A, the process involves a step ofproviding a segment of external tubing 150 having a proximal end (notshown), a distal end 500 and a lumen therethrough 502 having a centeraxis 504. The tubing 150 is typically in the range of 10 to 150 mm inlength and has an outer diameter in the range of 100 to 2000 microns.For applicability to specific procedures, the tubing may have an outerdiameter within one of three general ranges, 250 μm to 500 μm, 400 μm to800 μm, and 800 μm to 1200 μm. An optical light guide 505 having anlight transmitting end portion 112 is disposed within the tubing 150 sothat there is a luminal space 506 between the end portion 112 and thedistal end 500. The distance between the end portion 112 and the distalend is typically in the range of approximately 5 to 150 mm. The lightguide 505 may be a standard optical fiber suitable for transmittingultraviolet, visible, and near infrared light. The optical fiber isstripped of its buffer to expose at one end thereof a length of claddingand core which includes the light transmitting end portion 112. Thediameter of the cladding and core together is typically in the range of50-1900 microns. FIG. 11B illustrates a step of creating a first region510 by injecting a first medium 512 into the luminal space 506 betweenthe end portion 112 and the distal end 500. The first medium 512 maycomprise a transparent medium having substantially optically clearproperties, it may include scattering particles 513 (as shown) providinga desired light scattering power, or it may provide scatteringproperties by other means. Such mediums may include titanium dioxide,barium sulfate, powder quartz (SiO₂), aluminum oxide (Al₂O₃),polystyrene microspheres, silica microspheres, powdered diamond,zirconium oxide, ditantalum pentoxide, calcium hydroxyapatite, and acombination of any of these to name a few. The medium 512 may beinjected through an injection tube 514 or any other means suitable forinjecting such a medium. FIG. 11C illustrates a step of creating asecond region 520 by injecting a second medium 522 into the distal end500 of the external tubing 150 wherein the second region 520 has aconical shape. The second medium 522 has optical properties which differfrom the first medium 512. For example, the second medium 522 mayinclude optical particles 513 having a concentration which differs fromthat in the first medium 512. As the second medium 522 is injected intothe tubing 150, the second medium 522 essentially pushes the firstmedium 512 through the tubing 150 toward the end portion 112. Fluidflowing through and filling a horizontal tube are acted on by a numberof forces including inertia and friction. When a fluid flows into atube, such as by injection, a boundary layer starts at the entrance andgrows continuously until it cross-sectionally fills the tube. Theboundary layer is the region in which the velocity of the fluid variesfrom 0 to V (a maximum velocity). Thus, the velocity is close to zeronear the walls of the tubing 150 and reaches a maximum near the centralaxis 504. Since the second medium 522 is traveling at a higher velocitynear the central axis 504 of the lumen 502, the second region 520 formsa conical shape wherein the apex 524 is directed toward the end portion112. Displaced first medium 512 is pushed toward the end portion 112. Asshown, venting ports 526 through the external tubing 150 may be locatednear the end portion 112 so that air and/or excess medium may escapethrough the ports 526 as illustrated by arrows.

FIG. 11D illustrates a step of creating a third region 530 by injectinga third medium 532 into the distal end 500 of the external tubing 150wherein the third region 530 has a conical shape. The third medium 532has optical properties which differ from the second medium 522 but maybe the same as the first medium 512. Similar to the step of injectingthe second medium 522, injection of the third medium 532 into the tubing150 essentially pushes the second medium 522 and first medium 512through the tubing 150 toward the end portion 112. Since the thirdmedium 532 is traveling at a higher velocity near the central axis 504of the lumen 502, the third region 530 forms a conical shape wherein theapex 524 is directed toward the end portion 112. It may be appreciatedthat the length and shape of the cones may be controlled by the methodof injection, including speed of injection, angle and position of theinjection tube 514 and a variety of other variables. In addition,regions may be non-conical shaped by using other methods of injection.In this case, a diffuser tip 120 as shown in FIG. 8 may be producedwherein a non-conical region, the third region 304, is followed by aconical region, the fourth region 306, which is in turn followed by anon-conical region, the fifth region 308. Further, conical regions, suchas the first region 310 in FIG. 9, wherein the apex 158 is not directedtoward the end portion 112 may be produced by injecting material throughthe tubing 150 wall toward the distal end 124 or by producing thediffuser tip 120 itself and then connecting the diffuser tip 120 to thelight guide 102.

In any case, the above process steps may be repeated to create anynumber of regions in the diffuser tip 120. In the end, lumen 502 of theexternal tubing 150 will be filled with material. An example of such adiffuser tip 120 is illustrated in FIG. 11E. In addition, radiopaquemarker bands 550 have been added to aid in visualization underfluoroscopic conditions. Such bands 550 may be applied to the outersurface of the external tubing 150 or may be located within the tubing150. Alternatively, other radiopaque markings may be used, such aspaint, or an injected medium may be comprised of a material havingradiopacity properties or a material having a high concentration ofscattering particles with radiopacity properties, such as Bariumsulfate.

Referring to FIG. 12, the light transmission and diffusion apparatus 100may optionally include a guidewire tubing 600 having a distal end 602, aproximal end 604, and a lumen 606 therethrough through which a guidewire608 may pass. Typically, the guidewire lumen 606 is disposed along anaxis parallel to the central axis, such as when the guidewire tubing 600is disposed along the outside of the external tubing 150. The guidewirelumen 606 and may extend from the distal end 124 of the diffuser tip 120to the proximal end 104 (not shown) of the light guide 102 or to anylocation therebetween. Often, the distal end 602 of the guidewire lumen606 is aligned with the distal end 124 of the diffuser tip 120 and theproximal end 604 of the guidewire lumen 606 is located in the range of20 to 30 cm from the distal end 602. Such an arrangement provides a“monorail” system which provides a number of benefits during treatmentof a target site. In particular, the monorail system allows theguidewire 608 to be positioned within the guidewire tubing 600 duringdelivery of light therapy to the target site. In the area of thediffuser tip 120, the guidewire tubing 600 is comprised of a transparentmaterial that allows passage of visible light, particularly 730 nmlight, so that the guidewire tubing 600 will not interfere with thedelivery of light to the target region. Depending on the position andmaterial of the guidewire 608, the guidewire 608 may possibly obstructlight in this area but any possible effects on the therapeutic indexwould be within acceptable limits. Guidewire tubing 600 along any otherportion of the apparatus 100 may be comprised of the same transparentmaterial or it may be opaque, colored or have other properties. Inaddition, the guidewire tubing 600 may be a separate tube which isaffixed or adhered to the outside of the external tubing 150, which mayextend from the distal end 124 to the proximal end 104, or the guidewirelumen 606 may be formed as an extruded lumen within the walls of theapparatus 100.

FIGS. 13, 14, 15A-15B and 16A-16B illustrate methods of using thepresent invention. In particular, such embodiments illustrate methods ofperforming photodynamic therapy at a target site within a body lumen. Itmay be appreciated that the present invention may also be usedinterstitially or in non-cylindrical body cavities and may be used forpurposes other than photodynamic therapy. FIG. 13 illustrates across-sectional view of a target site TS within a body lumen L. In thiscase, the target site TS is a stenosis of atheromatous material within ablood vessel BV. As shown, a photosensitive compound 702 has beenintroduced into the target site TS to be activated by delivered light.The target site TS may be accessed by any means appropriate and aguidewire 608 may be positioned through the target site TS as shown.When accessing a target site TS in a blood vessel BV, a percutaneousapproach is often used such that a location of the vasculature remotefrom the target site TS is accessed through the skin, such as usingneedle access as in the Seldinger technique or by performing a surgicalcut down procedure or minimally invasive procedure. In any case, theability to percutaneously access the remote vasculature and position aguidewire therein is well-known and described in the patent and medicalliterature.

Referring to FIG. 14, the distal end 124 of the diffuser tip 120 of thelight transmission and diffusion apparatus 100 is introduced to thetarget site TS. In this case, the apparatus 100 is tracked over theguidewire 608 and positioned such that the diffuser tip 120 ispositioned within the target site TS. The apparatus 100 is then coupledto light radiation, such as from a light source 110, so that lightreceived by the diffuser tip 120 is delivered to the target site TS, asillustrated by arrows. Such light delivery activates the photosensitivecompound 702 causing therapeutic effects. Alternatively, as shown inFIG. 15A, a catheter 720, such as a Transit™ catheter, may be positionedwithin the target site TS by tracking over the guidewire 608. Typicallythe catheter 720 will have a single lumen, be compatible with 0.018″guidewires and have a floppy distal segment. The guidewire 608 is thenremoved and the apparatus 100 may then be introduced through thecatheter 720 so that the diffuser tip 120 is also positioned within thetarget TS, as shown in FIG. 15B. The apparatus 100 may then deliverlight to the target site TS wherein the light travels radially throughthe walls of the catheter 720. In this case, the catheter 720 iscomprised of a transparent material, to allow transmission of light, ora material having optical scattering properties. Alternatively, thecatheter 720 may be retracted while the apparatus 100 remains in place.In this case, light received by the diffuser tip 120 is delivered to thetarget site TS as illustrated in FIG. 14.

Referring to FIG. 16A, a balloon catheter 750 having a balloon 752mounted on its distal end 754 may be positioned within the target siteTS by tracking over the guidewire 608. In this example, the balloon 752is positioned within the target site TS as desired to perform anangioplasty procedure. As shown in FIG. 16B, the balloon 752 is theninflated with inflation fluid 756 thereby opening up the stenosis bycompressing the atheromatous material against the walls of the bloodvessel BV. While the balloon 752 is inflated, the guidewire 608 may ormay not be removed and the apparatus 100 may be introduced through theballoon catheter 750 so that the diffuser tip 120 is also positionedwithin the target TS, as shown in FIG. 16B. The apparatus 100 may thendeliver light to the target site TS wherein the light travels radiallythrough the balloon 752. In this case, the materials comprising theballoon catheter 750, balloon 752 and the inflation fluid 756 aretransparent, to allow transmission of light, or have optical scatteringproperties. It may be appreciated that some materials may be transparentwhile others have optical scattering properties. Alternatively, theballoon 752 may be deflated and the balloon catheter 750 may beretracted while the apparatus 100 remains in place. In this case, lightreceived by the diffuser tip 120 is delivered to the target site TS asillustrated in FIG. 14.

Referring now to FIG. 17, kits 800 according to the present inventioncomprise at least a light transmission and diffusion apparatus 100 andinstructions for use IFU. Optionally, the kits 800 may further includeany of the other components described above, such as a catheter 720, aballoon catheter 750, a guidewire 608, and a light source 110. Theinstructions for use IFU will set forth any of the methods as describedabove, and all kit components will usually be packaged together in apouch 802 or other conventional medical device packaging. Usually, thosekit components, such as the apparatus 100, which will be used inperforming the procedure on the patient will be sterilized andmaintained within the kit. Optionally, separate pouches, bags, trays orother packaging may be provided within a larger package, where thesmaller packs may be opened separately to separately maintain thecomponents in a sterile fashion.

Although the foregoing invention has been described in some detail byway of illustration and example, for purposes of clarity ofunderstanding, it will be obvious that various alternatives,modifications and equivalents may be used and the above descriptionshould not be taken as limiting in scope of the invention which isdefined by the appended claims.

1-90. (canceled)
 91. A light transmission and diffusion apparatuscomprising: a light guide having a proximal end and distal end, theproximal end adapted for coupling to a light source and the distal endhaving a light-transmitting end portion; and a diffuser tip having aproximal end enclosing said end portion and a distal end, the diffusertip comprising at least a first region and a second region, the secondregion comprising a second light scattering medium having a secondconcentration of scattering particles and wherein the second region hasa conical shape and is proximal to the distal end of the diffuser tip.92. An apparatus as in claim 91, wherein the first region comprises afirst light scattering medium having a first concentration of scatteringparticles.
 93. An apparatus as in claims 91 or 92, wherein the first andsecond regions are positioned and their light scattering mediums andconcentrations of scattering particles are chosen such that the diffusertip produces a substantially uniform pattern of illumination duringlight transmission.
 94. An apparatus as in claim 93, wherein thesubstantially uniform pattern of illumination is within approximately+/−20% uniformity.
 95. An apparatus as in claim 93, wherein thesubstantially uniform pattern of illumination comprises light ofessentially the same intensity from near the proximal end if thediffuser tip to near the distal end of the diffuser tip.
 96. Anapparatus as in claims 91 or 92, wherein the regions are positioned andtheir light scattering mediums and concentration of scattering particlesare chosen such that the diffuser tip produces a pattern of illuminationduring light transmission which has an intensity at its proximal anddistal ends which is greater than the intensity therebetween.
 97. Anapparatus as in claim 92, wherein the second region is distal to thefirst region.
 98. An apparatus as in claim 97, wherein the secondconcentration of scattering particles is greater than the firstconcentration of scattering particles.
 99. An apparatus as in claim 98,wherein the second region is oriented so its apex is directed toward thelight-transmitting end portion.
 100. An apparatus as in claim 92,wherein the diffuser tip further comprises a third region comprising athird light scattering medium having a third concentration of scatteringparticles and wherein the third region has a conical shape.
 101. Anapparatus as in claim 100, wherein the third region is oriented so itsapex is directed toward the light-transmitting end portion and is distalto and nested within the second portion.
 102. An apparatus as in claim101, wherein the third concentration of scattering particles is greaterthan the second concentration of scattering particles.
 103. An apparatusas in claim 100, wherein the diffuser tip further comprises a fourthregion comprising a fourth light scattering medium having a fourthconcentration of scattering particles and wherein the fourth region hasa conical shape, wherein the fourth region is oriented so its apex isdirected toward the light-transmitting end portion and is distal to andnested within the third portion and wherein the fourth concentration ofscattering particles is greater than the third concentration ofscattering particles.
 104. An apparatus as in claim 92, 100 or 103,wherein each region comprises a different light scattering medium. 105.An apparatus as in claim 92, 100 or 103, wherein each region comprises adifferent concentration of scattering particles.
 106. An apparatus as inclaim 92, 100 or 103, wherein each region comprises scattering particleshaving a different size.
 107. An apparatus as in claim 92, 100 or 103,wherein each region comprises scattering particles having a differentrefractive index.
 108. An apparatus as in claim 92, 100 or 103, whereineach region comprises scattering particles having different absorptionproperties.
 109. An apparatus as in claim 92, 100 or 103, wherein eachregion further comprises particles which are light absorbing,fluorescent or magnetic resonance imaging detectable.
 110. An apparatusas in claim 91, wherein the light scattering medium of the most distallypositioned region provides radiopacity under fluoroscopy.
 111. Anapparatus as in claim 110, wherein the light scattering medium of themost distally positioned region comprises barium sulfate, ditantalumpentoxide or calcium hydroxyapatite.
 112. An apparatus as in claim 91,wherein the regions are positioned and their light scattering mediumsand concentration of scattering particles are chosen such that all lighttransmitted to the most distally positioned region is substantiallydiffused radially outwardly.
 113. An apparatus as in claim 112, whereinthe light scattering mediums comprise titanium dioxide, barium sulfate,powder quartz, aluminum oxide, polystyrene microspheres, silicamicrospheres, powdered diamond, zirconium oxide, ditantalum pentoxide,calcium hydroxyapatite, or a combination of any of these.
 114. Anapparatus as in claim 91, wherein the diffuser tip has a maximum outsidediameter in the range of about 150 μm to 1200 μm.
 115. An apparatus asin claim 114, wherein the diffuser tip has a maximum outside diameter inthe range of about 250 μm to 1200 μm.
 116. An apparatus as in claim 114,wherein the diffuser tip has a maximum outside diameter of approximately250 μm to 500 μm.
 117. An apparatus as in claim 114, wherein thediffuser tip has a maximum outside diameter of approximately 800 μm to1200 μm.
 118. An apparatus as in claim 91, wherein the diffuser tipfurther comprises an external layer comprising light scatteringmaterial.
 119. An apparatus as in claim 91, wherein the distal end has arounded or short tapered shape.
 120. An apparatus as in claim 91,wherein the distal end terminates in a narrow elongated portion which isfloppy.
 121. An apparatus as in claim 91, further comprising a guidewirelumen.
 122. An apparatus as in claim 121, wherein the guidewire lumen isdisposed along an axis parallel to and offset from a central axis. 123.An apparatus as in claim 91, wherein the diffuser tip is adapted to beinsertable within a lumen in a catheter.
 124. An apparatus as in claim123, wherein the catheter has a balloon mounted thereon and the diffusertip is insertable to a position where the tip is surrounded by theballoon.